Method for producing 1-substituted 5-Hydroxypyrazoles

ABSTRACT

The invention relates to a process for preparing 1-substituted 5- and/or 3-hydroxypyrazoles of the formulae I and II                    
     in which R 1  is C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl or C 1 -C 4 -alkoxy, where these groups may be substituted by halogen, C 1 -C 4 -alkoxy, phenoxy, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkylthiocarbonyl or by a cyclic ring system having 3-14 ring atoms, which comprises reacting 
     an alkyl 3-alkoxyacrylate of the formula III                    
     in which R 2 , R 3  independently of one another are C 1 -C 6 -alkyl or C 3 -C 6 -cycloalkyl with a hydrazine of the formula IV                    
     in which R 1  is as defined above 
     a) at a pH of 6-11 to give 5-hydroxypyrazoles of the formula I or 
     b) at a pH of 11-14 to give 3-hydroxypyrazoles of the formula II.

This application is a 371 of PCT/EP99/08516 filed Nov. 6, 1994.

The present invention relates to a process for preparing 1-substituted5- and/or 3-hydroxypyrazoles of the formulae I and II, respectively

in which R¹ is C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,C₃-C₆-cycloalkyl or C₁-C₄-alkoxy, where these groups may be substitutedby halogen, C₁-C₄-alkoxy, phenoxy, C₁-C₆-alkoxycarbonyl,C₁-C₆-alkylthiocarbonyl or by a cyclic ring system having 3-14 ringatoms, which comprises [lacuna]

1-Substituted 5- and 3-hydroxypyrazoles are used as intermediates forpreparing pharmaceutics and crop protection agents, in particularherbicides, and are disclosed, for example, in WO96/26206, WO 97/23135,WO 97/19087, U.S. Pat. No. 5,631,210, WO 97/12885, WO 97/08164, ZA9510980, WO 97/01550, WO 96/31507, WO 96/30368, WO 96/25412 and U.S.Pat. No. 5,663,365.

Processes for their preparation are therefore of interest.

To date, the following syntheses are known as processes for preparinglower 1-alkyl-5-hydroxypyrazoles:

1. a preparation where 2-methyl-1-(p-toluenesulfonyl)-3-pyrazolidone or2-methyl-1-1-acetyl-pyrazolidone [sic] is hydrolyzed (J. Prakt. Chem.313 (1971), 115-128 and J. Prakt. Chem. 313 (1971), 1118-1124).

2. a variant in which alkyl 5-hydroxy-1-alkylpyrazole-4-carboxylate issynthesized by cyclization of a dialkyl alkoxymethylenemalonate withlower alkylhydrazines, an aqueous solution of mineral acid issubsequently added to this reaction product and hydrolysis anddecarboxylation are carried out simultaneously (see JP 61257974, JP60051175, JP 58174369, JP 58140073 and JP 58140074 and also U.S. Pat.No. 4,643,757).

3. a synthesis in which ethyl propiolate is reacted with methylhydrazineto give 5-hydroxy-1-methylpyrazole (Annalen 686 (1965), 134-144).

4. a synthesis route in which 3-hydrazinopropionic esters, which areformed by addition of hydrazine to acrylic esters, are reacted withaldehydes to give the corresponding hydrazones, which are subsequentlycyclized (see JP 06166666, JP 61229852 and JP 61268659 and also EP240001).

5. a synthesis variant in which a5-hydroxy-1-methylpyrazole-3-carboxylic acid is cleaved thermally (Chem.Ber. 109 (1976), 261).

6. a process in which 3-alkoxyacrylic esters are reacted withmethylhydrazine and ethylhydrazine to give 1-methyl-5-hydroxypyrazoleand 1-ethyl-5-hydroxypyrazole, respectively (see JP 189 271/86, EP-A-837058).

7. a process in which 2-haloacrylic esters are reacted with hydrazinederivatives to give 1-substituted 3-hydroxypyrazoles (see U.S. Pat. No.5,663,365).

The process of the 1st synthesis route mentioned above entails severalsteps and is complicated. Introduction and removal of a protecting groupis awkward, means an additional number of steps and reduces the yield.

The 2nd preparation possibility entails several steps; moreover, inaddition to the 1-alkyl-5-hydroxypyrazoles, the regioisomers of thetarget compound are formed at the same time, and they have to beseparated off from the target compounds in a complicated procedure.Furthermore, the synthesis is associated with a poor C yield since a C4building block is employed from which, at the end of the process, acarbon atom has to be cleaved off again.

In the 3rd synthesis variant, which describes only the preparation of1-methyl-5-hydroxypyrazole, it is unavoidable to employ highlyhyperstoichiometric amounts of methylhydrazine, thus rendering theprocess uneconomical. In addition, the isomer3-hydroxy-1-methylpyrazole, which is also formed, has to be separatedoff from 1-methyl-5-hydroxypyrazole in a complicated procedure duringpurification. Furthermore, owing to the high cost of propiolic ester,this process is uneconomical.

The process of the 4th alternative entails several steps and iscomplicated. The last step of the complex process affords only pooryields and a large number of byproducts.

The thermal cleavage of the 5th synthesis route requires a hightemperature, and the yield of 6% is very low.

The 6th synthesis route, which describes only the preparation of1-methyl-5-hydroxypyrazole, uses 3-alkoxyacrylic esters which aredifficult to prepare and are expensive. The preparation of3-alkoxyacrylic esters is carried out by reaction of methanol withexpensive propiolic esters (Tetrahedron Lett. 24 (1983), 5209, J. Org.Chem. 45 (1980), 48, Chem. Ber. 99 (1966), 450, Chem. Lett. 9 (1996),727-728), by reacting α,α-dichlorodiethyl ether, which is expensive anddifficult to synthesize, with bromoacetic esters (Zh. Org. Khim. 22(1986), 738), by reaction of bromoacetic esters with trialkyl formates(Bull. Soc. Chim. France N 1-2 (1983), 41-45) and by elimination ofmethanol from 3,3-dialkoxypropionic esters (DE 3701113) (obtainable byreacting the expensive methyl propiolate with methanol (J. Org. Chem. 41(1976), 3765)), by reacting 3-N-acetyl-N-alkyl-3-methoxypropionic esterswith methanol (J. Org. Chem. 50 (1985), 4157-4160, JP 60-156643), byreacting acrylic esters with alkylamines and acetic anhydride (J. Org.Chem. 50 (1985), 4157-4160), by reacting ketene with trialkylorthoformate (DK 158462), by palladium- and simultaneouslycopper-catalyzed reaction of acrylic esters with methanol (DE4100178.8), by reaction of trichloroacetyl chloride with vinyl ethylether (Synthesis 4 (1988), 274), by reactingα,α,α-trichloro-β-methoxybutene-2-one with methanol (Synthesis 4 (1988),274) and by reacting the sodium salts of 3-hydroxyacrylic esters withalcohols (DB 3641605). The fact that the 3-alkoxyacrylic esters aredifficult to obtain thus renders the synthesis according to 6uneconomical. Moreover, JP 189 271/86 only describes the isolation ofthe 5-hydroxy-1-methylpyrazole as the hydrochloride, but no details aregiven for the isolation and purification of the free base. Efforts toapply the reaction conditions described in JP 189 271/86 and to isolatethe free base result in only very poor yields which are uneconomical fora preparation of hydroxypyrazoles on an industrial scale.

The 7th synthesis route has the disadvantage that only3-hydroxypyrazoles can be prepared, and no 5-hydroxypyrazoles.Consequently, these synthesis routes are not satisfactory as economicaland efficient processes for preparing 1-substituted 5- and3-hydroxypyrazoles.

Furthermore, there is no process known from the prior art which permitspreparation of both the 1-substituted 5- and the 3-hydroxypyrazole bysimple variation of the process parameters.

Moreover, there is no process known from the prior art which leads tothe desired 1-substituted 5- and 3-hydroxypyrazoles from simple startingmaterials such as an alkyl vinyl ether.

It is an object of the present invention to provide a process whichallows the preparation of 1-substituted 5-hydroxypyrazoles and/or3-hydroxypyrazoles in [sic] by changing the process parameters.

It is another object of the present invention to provide a process forpreparing 1-substituted 5-hydroxypyrazoles and/or 3-hydroxypyrazolesfrom easily obtainable starting materials which does not have theabovementioned disadvantages of the prior art processes.

We have found that this object is achieved by the process according tothe invention for preparing 1-substituted 5- and/or 3-hydroxypyrazolesof the formulae I and II

in which R¹ is C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,C₃-C₆-cycloalkyl, C₁-C₄-alkoxy or phenoxy, where these groups may besubstituted by halogen, C₁-C₄-alkoxy, C₁-C₆-alkoxycarbonyl,C₁-C₆-alkylthiocarbonyl or by a cyclic ring system having 3-14 ringatoms, by reacting

an alkyl 3-alkoxyacrylate of the formula III

in which R², R³ independently of one another are C₁-C₆-alkyl orC₃-C₆-cycloalkyl with a hydrazine of the formula IV

in which R¹ is as defined above

a) at a pH of 6-11 to give 5-hydroxypyrazoles of the formula I or

b) at a pH of 11-14 to give 3-hydroxypyrazoles of the formula II.

Moreover, we have found a process starting from easily obtainable alkylvinyl ethers for preparing the alkyl 3-alkoxyacrylate of the formula IIIby reacting

c) an alkyl vinyl ether of the formula V

 in which R² is as defined in claim 1 with phosgene VIa, “diphosgene”VIb or “triphosgene” VIc

to give an acyl chloride of the formula VII

d) converting this by elimination of hydrogen chloride into thecorresponding 3-alkoxyacryloyl chloride of the formula VIII

 and

e) esterifying this with an alcohol of the formula IX

 in which R³ is as defined in claim 1 to give the corresponding alkyl3-alkoxyacrylate of the formula III.

Surprising and novel in the process according to the invention are thefacts that 5- or 3-hydroxypyrazoles of the formulae I and II,respectively, can be prepared selectively by appropriate choice of thereaction conditions, and that easily obtainable starting materials canbe employed.

Preferred embodiments of the process according to the invention areshown in the subclaims and in the description below.

Step a):

The reaction of the alkyl 3-alkoxyacrylates of the formula III withhydrazines of the formula IV to give the 1-substituted5-hydroxypyrazoles is generally carried out by initially charging one ofthe two reaction participants in a suitable solvent and metering in thesecond reaction participant at from −30° C. to 100° C. By addition of abase, the pH is kept at 7-11, preferably 8-11, particularly preferably9-11. Suitable bases are, for example, alkali metal and alkaline earthmetal hydroxides, such as sodium hydroxide and potassium hydroxide, andalso tertiary amines.

Preferred bases are alkali metal and alkaline earth metal hydroxides,such as sodium hydroxide and potassium hydroxide. The molar ratio ofalkyl 3-alkoxyacrylate III to hydrazine IV is from 1:1 to 1:10,preferably from 1:1 to 1:8. This ratio can be reduced from 1:10 to 1:1by addition of bases.

According to a preferred procedure, only the solvent is initiallycharged, and the hydrazine IV and the alkyl 3-alkoxyacrylate III areadded simultaneously dropwise over a period of from 10 min to 10 h,preferably 1-4 h. The particular advantage of this parallel additionconsists in the fact that this allows the pH of the reaction mixture tobe kept constant at approximately 10, without addition of a base beingrequired. The maintenance of this pH, in turn, is essential for theregioselectivity of the reaction. When a pH of 10, for example, ismaintained, it is possible to obtain regioisomer ratios I:II of morethan 300:1.

Moreover, it has been found to be favorable to reduce the temperatureafter a certain reaction time and to allow the reaction to go tocompletion at a correspondingly lower temperature.

Suitable solvents or diluents are, for example, water, aliphatichydrocarbons, such as pentane, hexane, cyclohexane and petroleum ether,aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, halogenatedhydrocarbons, such as methylene chloride, chloroform and chlorobenzene,alcohols, such as methanol and ethanol, and also ethers, such as diethylether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole andtetrahydrofuran, and nitriles, such as acetonitrile and propionitrile.It is of course also possible to use mixtures of the abovementionedsolvents.

Preferred solvents are, for example, water, alcohols, such as methanoland ethanol, ethers, such as diethyl ether, diisopropyl ether,tert-butyl methyl ether, dioxane, anisole, diethylene glycol dialkylethers and tetrahydrofuran, and mixtures of these.

The hydrazines IV can be employed both neat and in the form of theiraqueous solutions, some of which are commercially available.

Step b):

The reaction of the alkyl 3-alkoxyacrylates III with hydrazines IV togive the 1-substituted 3-hydroxypyrazoles II is preferably carried outby initially charging the hydrazine IV in a suitable solvent andmetering in the alkyl 3-alkoxyacrylate VIII at from −30° C. to 100° C.,preferably at 10-40° C., over a period of from 10 min to 10 h,preferably 1-4 h. During this addition, the pH is kept between 11 and14, preferably at 12-13, in particular at 12, by addition of a base. Byadjusting the pH to the last-mentioned values, it is possible to obtainthe 1-substituted 3-hydroxypyrazoles II in high regioselectivity.Suitable bases are alkali metal and alkaline earth metal hydroxides,such as sodium hydroxide and potassium hydroxide, and tertiary amines.Preferred bases are alkali metal and alkaline earth metal hydroxides.Suitable solvents are those mentioned in step a).

Step c):

The overall process according to the invention starts with alkyl vinylethers of the formula V which are initially reacted at from −78° C. to100° C., preferably from -10° C. to 80° C., in particular from 20° C. to60° C., with an acyl chloride of the formula VIa, VIb or VIc, to givethe corresponding acyl chloride of the formula VII.

The reaction can be carried out without using solvents or diluents ifthe reaction partners are liquid at the reaction temperature. However,it is also possible to carry out the reaction in an aprotic solvent ordiluent.

Suitable solvents or diluents are, for example, aliphatic hydrocarbons,such as pentane, hexane, cyclohexane and petroleum ether, aromatichydrocarbons, such as toluene, o-, m- and p-xylene, halogenatedhydrocarbons, such as methylene chloride, chloroform and chlorobenzene,and also ethers, such as diethyl ether, diisopropyl ether, tert-butylmethyl ether, dioxane, anisole and tetrahydrofuran, and nitrites, suchas acetonitrile and propionitrile. It is of course also possible to usemixtures of the abovementioned solvents.

Particularly preferably, the reaction is carried out in the absence of asolvent, or in aromatic hydrocarbons such as toluene as solvent.

The reaction partners V and VI are generally reacted with each other ina ratio of from 0.1:1 to 1:1 mol of V/VIa, VIb or VIc, preferably from0.2:1 to 0.8:1 mol of V/VIa, VIb or VIc, in particular from 0.4:1 to0.6:1 mol of V/VIa, VIb or VIc.

Since both the halides VI and the acyl chloride VII which is formed areunstable toward moisture, it is recommended to carry out the reactionunder exclusion of water, preferably under an atmosphere of protectivegas (nitrogen or another inert gas).

In the case of the reaction of V with VIb or VIc, it may be advantageousto accelerate the reaction by addition of catalytic amounts of atertiary amine, such as triethylamine or pyridine.

Step d):

At 30-80° C., the resulting acyl chloride VII eliminates hydrogenchloride (HC1), giving the corresponding 3-alkoxyacryloyl chloride VIII.

For this step of the reaction, it may be advantageous to remove thehydrogen chloride which is formed from the reaction volume, by applyingslightly reduced pressure or by passing inert gas through the reactionmixture or the reaction vessel, thus removing the hydrogen chloridewhich is formed.

The excess chloride of the formula VIa, VIb or VIc can be recycled intothe synthesis and has to be removed in any case for the isolation of thepure product of value. This also applies to any catalysts which may havebeen added.

The resulting crude 3-alkoxyacryloyl chlorides VIII can be isolated inpure form by distillation or rectification.

However, they can also be converted directly, without furtherpurification, into the corresponding alkyl 3-alkoxyacrylates III.

Step e):

The acyl chlorides VIII are generally esterified by adding the alcoholIX dropwise to the acyl chloride VIII, at from −20 to 80° C., preferablyat 0-50° C., over a period of 0.5-8 h, preferably 1-6 h, and purifyingthe resulting alkyl 3-alkoxyacrylate III by continuous or batchwisedistillation or rectification.

However, it is also possible to carry out the reaction in an aproticsolvent or diluent. Suitable solvents or diluents are, for example,aliphatic hydrocarbons, such as pentane, hexane, cyclohexane andpetroleum ether, aromatic hydrocarbons, such as toluene, o-, m- andp-xylene, halogenated hydrocarbons, such as methylene chloride,chloroform and chlorobenzene, and also ethers, such as diethyl ether,diisopropyl ether, tert-butyl methyl ether, dioxane, anisole andtetrahydrofuran, and nitriles, such as acetonitrile and propionitrile.It is of course also possible to use mixtures of the abovementionedsolvents.

It is recommended to carry out the reaction in the presence of hydrogenchloride-binding reagents, such as, for example, pyridine. It is ofcourse also possible to use the last-mentioned reagents as solvents.

With respect to the intended use of the 1-substituted 5- and/or3-hydroxypyrazoles of the formulae I and II, the following radicals aresuitable substituents:

R¹

C₁-C₄-alkyl, such as methyl, ethyl, n-propyl, 1-methylethyl, butyl,1-methylpropyl, 2-methylpropyl and 1,1-dimethylethyl;

C₁-C₆-alkyl, such as C₁-C₄-alkyl as mentioned above, and also pentyl,1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl,1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-thylbutyl,2-ethylbutyl, 1,1,2-trimethylpropyl, 1-ethyl-1-methylpropyl and1-ethyl-3-methylpropyl;

in particular methyl, ethyl, 1-methylethyl, 1-methylpropyl,2-methylpropyl, 1,1-dimethylethyl and 1,1-dimethylpropyl;

C₂-C₆-alkenyl, such as 2-propenyl, 2-butenyl, 3-butenyl,1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl,4-pentenyl, 3-methyl-2-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl,1-methyl-3-butenyl, 2-methyl-4-butenyl, 3-methyl-3-butenyl,1,1-dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-2-propenyl,2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-2-pentenyl,2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl,1-methyl-3 pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl,4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl,3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl,1,1-dimethyl-3-butenyl, 1,2-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl,2,2-dimethyl-3-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl,1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-2-butenyl,2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl,1-ethyl-1-methyl-2-propenyl and 1-ethyl-2-methyl-2-propenyl,

in particular 1-methyl-2-propenyl, 1-methyl-2-butenyl,1,1-dimethyl-2-propenyl and 1,1-dimethyl-2-butenyl;

C₂-C₆-alkynyl, such as propargyl, 2-butynyl, 3-butenyl [sic],2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-3-butynyl,2-methyl-3-butynyl, 1-methyl-2-butynyl, 1,1-dimethyl-2 propynyl,1-ethyl-2-propynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl,1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl,3-methyl-4-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl,1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl,1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and1-ethyl-1-methyl-2-propynyl;

C₃-C₆-cycloalkyl, such as, for example, cyclopropyl, cyclobutyl,cyclopentyl and cyclohexyl,

in particular cyclopropyl and cyclohexyl;

C₁-C₄-alkoxy, such as methoxy, ethoxy, n-propoxy, 1-methylethoxy,n-butoxy, 1-methylpropoxy, 2-methylpropoxy and 1,1-dimethylethoxy,

in particular C₁-C₃-alkoxy, such as methoxy, ethoxy, isopropoxy;

where these groups may be unsubstituted or substituted by one to fivehalogen atoms, such as fluorine, chlorine, bromine and iodine,preferably fluorine and chlorine, C₁-C₄-alkoxy, phenoxy,C₁-C₆-alkoxycarbonyl, C₁-C₆-alkylthiocarbonyl or a cyclic ring systemhaving 3-14 ring atoms, where the substituents are as defined below:

C₁-C₆-alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, 1-methylethoxycarbonyl, n-butoxycarbonyl,1-methylpropoxycarbonyl, 2-methylpropoxycarbonyl and1,1-dimethylethoxycarbonyl, in particular methoxycarbonyl;

C₁-C₆-alkylthiocarbonyl, such as methylthiocarbonyl, ethylthiocarbonyl,n-propylthiocarbonyl, in particular methylthiocarbonyl;

C₁-C₄-haloalkyl: a C₁-C₄-alkyl radical as mentioned above which ispartially or fully substituted by fluorine, chlorine, bromine and/oriodine, i.e., for example, chloromethyl, dichloromethyl,trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl,chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl,2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl,2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl,2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl,2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl,2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl,2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl,3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl,1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl,1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyland nonafluorobutyl;

A cyclic ring system having 3-14 ring atoms means, for example, thefollowing groups: C₃-C₁₄-cycloalkyl, C₃-C₁₄-cycloalkenyl, aromaticgroups, such as phenyl, naphthyl, and their partially hydrogenatedderivatives. The cyclic ring systems may furthermore representheterocyclic ring systems in which one, two or three carbon atoms may bereplaced by heteroatoms, such as, for example, O, N, S. In principle,the cyclic ring systems may be aromatic or partially or fullyhydrogenated. The cyclic ring systems can be substituted at will.Suitable substituents are, for example, C₁-C₆-alkyl, C₁-C₄-haloalkyl,C₁-C₄-alkoxy, halogen, cyano, nitro, hydroxyl, thionyl, sulfoxyl,sulfonyl, C₁-C₄-alkylsulfonyl, amino, C₁-C₄-alkylamino anddi-C₁-C₄-alkylamino.

Preference is given to cyclic ring systems from the group consisting ofC₁-C₆-cycloalkyl, phenyl, a 5- to 6-membered heterocyclic, saturated orunsaturated radical containing one to three heteroatoms selected fromthe group consisting of O, N and S. each of which may be substituted asmentioned above.

Particular preference is given to C₁-C₆-cycloalkyl and phenyl which maybe substituted as mentioned above.

A very particularly preferred cyclic ring system is phenyl which may besubstituted as mentioned above.

R², R³ independently of one another [lacuna] C₁-C₆-alkyl as mentionedabove or C₃-C₆-cycloalkyl, preferably C₁-C6-alkyl.

EXAMPLES Example 1

3-Ethoxyacryloyl Chloride

At 35° C., 110 g (1.1 mol) of phosgene are introduced into a solution of72 g (1 mol) of ethyl vinyl ether in 100 g of toluene over a period of1.5 h. The mixture is subsequently stirred at 60° C. for 4 hours. Duringthe entire reaction time, phosgene and ethyl vinyl ether are recondensedinto the reaction mixture using a dry-ice condenser at −78° C. Thesolution is subsequently stripped of phosgene and room temperature, andthe solvent is removed by distillation. Vacuum distillation at 36°C./0.4 mbar gives 88 g (66%) of the product of value.

Example 2

3-Isobutoxyacryloyl Chloride

100 g (1 mol) of isobutyl vinyl ether are initially charged in a 2 1stirred apparatus and heated to 50-55° C. 1024 g (10.4 mol) of phosgeneare subsequently introduced over a period of 21 h, and 900 g (9 mol) ofisobutyl vinyl ether are added dropwise over a period of 19 h. After anextra reaction time of 0.5 hours, the reaction mixture is heated to 80°C. with nitrogen stripping to eliminate hydrogen chloride. Thelow-boilers are then distilled off via a 15 cm Vigreux column, and theresidue is analyzed by gas chromatography. This gives 1551 g (80%) ofcrude isobutoxyacrylolyl chloride (calc. 100%).

Example 3

3-Cyclohexyloxyacryloyl Chloride

50 g (0.5 mol) of phosgene are condensed into a stirred apparatus fittedwith −78° C.-cooling. Over a period of 3 hours, 50.5 g (0.4 mol) ofcyclohexyl vinyl ether are subsequently added dropwise at 20° C. Themixture is then stirred at 50° C. for 5 hours. The excess phosgene isflushed out with nitrogen, and the crude product is worked up bydistillation. At 110° C./2.5 mbar, 66.4 g (88%) of the product of valuewere obtained.

Example 4

Isobutyl Isobutoxyacrylate

100 g (1.0 mol) of isobutyl vinyl ether are initially charged in a 500ml stirred apparatus and heated to 50-55° C. 113 g (1.15 mol) ofphosgene are subsequently introduced over a period of 11 h. After anextra reaction time of 1.5 h, the reaction mixture is stripped phosgenefree at 50-55° C. by introduction of nitrogen. The mixture issubsequently allowed to cool to room temperature, and and [sic] 60.7 g(0.82 mol) of isobutanol are added dropwise. After the addition hasended, the resulting reaction mixture is rectified. This gives 150.4 g(75%) of isobutyl 3-isobutoxyacrylate of b.p. 97° C. at 2.5 mbar.

Example 5

5-Hydroxy-1-methylpyrazole from Methyl 3-methoxyacrylate andMonomethylhydrazine (35%)

In a 250 ml flask, 106.2 g (0.808 mol) of 35% strength aqueousmonomethylhydrazine and 47.82 g (0.404 mol) of methyl 3-methoxyacrylateare simultaneously metered at 25° C. and over a period of 25 min into 70g of methanol. The reaction mixture is stirred at 25° C. for 2 hours andthen analyzed by gas chromatography. The yield is 95% at 100% conversion(in each case based on methyl 3-methoxyacrylate).

Isomer ratio: (5-hydroxy isomer:3-hydroxy isomer)≧200:1

Example 6

5-Hydroxy-1-methylpyrazole from Isobutyl 3-isobutoxyacrylate andMonomethylhydrazine (35%)

In a 0.75 1 reactor, 287.5 g (2.18 mol) of 35% strength aqueousmonomethylhydrazine and 175.2 g (0.875 mol) of isobutyl3-isobutoxyacrylate are simultaneously metered at 25° C. and over aperiod of 1.5 hours into 202 g of methanol. The reaction mixture isstirred at 25° C. for 6.75 hours, then cooled to 5° C. for 16 hours andsubsequently analyzed by gas chromatography. The yield is 88% at 98%conversion (in each case based on isobutyl isobutoxyacrylate).

Isomer ratio: (5-hydroxy isomer:3-hydroxy isomer)≧300:1

Example 7

3-Hydroxy-1-methylpyrazole from Methyl 3-methoxyacrylate andMonomethylhydrazine (35%)

In a 250 ml flask, 70 g of methanol and 60.5 g (0.46 mol) of 35%strength aqueous monomethylhydrazine are initially charged at 25° C. Atthe same temperature, 47.8 g (0.40 mol) of methyl 3-methoxyacrylate aremetered in over a period of 25 min. By parallel addition of 17% strengthaqueous NaOH solution, the pH of the reaction mixture during the meteredaddition of the methyl methoxyacrylate and during the extra stirringtime (6 hours) is maintained at 12. Over this period of time, 97.5 g ofNaOH solution are consumed. The yield is 75% at 100% conversion.

Isomer ratio: (3-hydroxy isomer:5-hydroxy isomer)≧15:1

Example 8

1-Ethoxycarbonylmethyl-5-hydroxypyrazole from Methyl 3-methoxyacrylateand Ethyl Hydrazineacetate Hydrochloride

In a 2 1 round-bottomed flask, 85.5 g (0.55 mol) of ethylhydrazineacetate hydrochloride are initially charged in 770 ml ofmethanol at 25° C. At 60-65° C., 63.8 g (0.55 mol) of methyl3-methoxyacrylate are metered in over a period of 1.25 hours. After theaddition has ended, the mixture is refluxed for 2 hours and subsequentlyadjusted to a pH of 5 using 30% strength methanolic sodium methoxidesolution. The reaction mixture is subsequently analyzed by gaschromatography. The yield is 85% at 100% conversion.

Using the processes described above, the compounds below were preparedin a similar manner.

Constitution Physical data; 1H NMR data

m.p. 94° C. 1H NMR (d6-DMSO): 1.3 (t, 3H), 3.9 (q, 2 H), 5.3 (d, 1H),7.3 (d, 1H), 10.4 (brd., 1H).

b.p. (1 mbar): 114° C. 1H NMR (d6-DMSO): 0.8 (t, 3H), 1.6 (m, 2 H), 3.7(t, 2H), 5.3 (d, 1H), 7.0 (d, 1H).

b.p. (0.5 mbar): 107-108° C. 1H NMR (d6-DMSO): 0.9 (t, 3H), 1.2 (m, 2H), 1.7 (m, 2H), 3.8 (t, 2H), 5.2 (d, 1H), 7.0 (d, 1H), 9.1 (brd., 1H).

b.p. (2 mbar): 135° C. 1H NMR (d6-DMSO): 0.9 (d, 6H), 2.1 (sept., 1H),3.5 (d, 2H), 5.2 (d, 1H), 7.0 (d, 1H), 10.6 (brd., 1H).

1H NMR (d6-DMSO): 1.5 (s, 9H), 5.3 (d, 1 H), 7.0 (d, 1H), 10.6 (brd.,1H).

1H NMR (d6-DMSO): 5.1 (s, 2H), 5.3 (s, 1 H), 7.1-7.3 (m, 6H), 11.1(brd., 1H).

1H NMR (d6-DMSO): 4.7 (q, 2H), 5.4 (d, 1 H), 7.3 (d, 1H9, 11.4 (brd.,1H).

1H NMR (d6-DMSO): 1.2 (t, 2H), 4.1 (q, 2 H), 4.7 (s, 2H), 5.3 (d, 1H),7.2 (d, 1H), 11.2 (brd., 1H).

1H NMR (d6-DMSO): 1.0 (t, 6H), 3.3 (m, 2 H), 3.6 (m, 2H), 3.9 (d, 2H),4.7 (t, 1H), 5.3 (d, 1H), 7.1 (d, 1H), 11.0 (brd., 1H).

1H NMR (d6-DMSO): 1.1 (t, 6H), 1.9 (m, 2 H), 3.4 (m, 2H), 3.6 (m, 2H),3.9 (m, 2H), 4.5 (m, 1H), 5.3 (d, 1H), 7.1 (d, 1H), 11.0 (brd., 1H).

The 1-substituted 5- or 3-hydroxypyrazoles prepared by the processaccording to the invention are useful precursors for preparing, forexample, crop protection agents, such as herbicides. Herbicidesdisclosed in WO 96/26206 are, for example,

We claim:
 1. A process for preparing a 1-substituted 5- and/or3-hydroxypyrazole of the formulae I and II, respectively

in which R¹ is C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,C₃-C₆-cycloalkyl or C₁-C₄-alkoxy, where these groups may be substitutedby halogen, C₁-C₄-alkoxy, phenoxy, C₁-C₆-alkoxycarbonyl,C₁-C₆-alkylthiocarbonyl or by a cyclic ring system having 3-14 ringatoms, which comprises reacting c) an alkyl vinyl ether of the formula V

 in which R² is C₁-C₆-alkyl or C₃-C₆-cycloalkyl with phosgene VIa,“diphosgene” VIb or “triphosgene” VIc

to give an acyl chloride of the formula VII

d) converting this by elimination of hydrogen chloride into thecorresponding 3-alkoxyacryloyl chloride of the formula VIII

 and e) esterifying this with an alcohol of the formula IX

 in which R³ is C₁-C₆-alkyl or C₃-C₆-cycloalkyl to give thecorresponding alkyl 3-alkoxyacrylate of the formula III, and reactingsaid alkyl 3-alkoxyacrylate of the formula III

with a hydrazine of the formula IV

in which R¹ is as defined above a) at a pH of 6-11 to give5-hydroxypyrazoles of the formula I or b) at a pH of 11-14 to give3-hydroxypyrazoles of the formula II.
 2. A process as claimed in claim1, wherein the reaction in step a) is carried out at from −30° C. to100° C.
 3. A process as claimed in claim 1, wherein the reaction iscarried out in the presence of a base.
 4. A process as claimed in claim1, wherein the base used is an alkali metal hydroxide, alkaline earthmetal hydroxide or tertiary amine.
 5. A process as claimed in claim 2,wherein a solvent is initially charged and the alkyl 3-alkoxyacrylateIII and the hydrazine IV are simultaneously metered into the solvent. 6.A process as claimed in claim 5, wherein the solvent used is water, analcohol, an ether or a mixture of these.
 7. A process as claimed inclaim 1, wherein the reaction in step b) is carried out at from −30° C.to 100° C.
 8. A process as claimed in claim 7, wherein the reaction iscarried out in the presence of a base.
 9. A process as claimed in claim8, wherein the base used is an alkali metal hydroxide, alkaline earthmetal hydroxide, a tertiary amine or a mixture of these.
 10. A processas claimed in claim 1, wherein the reaction in step c) is carried out atfrom −78° C. to 100° C.
 11. A process as claimed in claim 1, wherein thealkyl vinyl ether V is reacted with phosgene VIa, diphosgene VIb ortriphosgene VIc in a molar ratio of from 0.1:1 to 1:1.
 12. A process asclaimed in claim 1, wherein the reaction in step d) is carried out atfrom 30° C. to 80° C.
 13. A process as claimed in claim 1, wherein theesterification in step e) is carried out at from −20° C. to 80° C.